2 

Mammalian Chronic Toxicity 

The original assessment identified the most sensitive chronic mammalian toxicity endpoint in the 

two-generation rat reproduction study as a NOAEL of 20 mg ai/kg-diet, based on parental 

thyroid weight increase and corresponding dose-related increase in the incidence of thyroid 

follicular epithelial cell hypertrophy/hyperplasia (MRID 48119967). EFED policy is to base risk 

quotient (RQ) calculations on the most sensitive endpoints that adversely affect reproduction, 

growth, and survival. Upon further review, the thyroid effects seen in the study did not result in 

adverse effects on reproduction, growth, or survival. Consequently, the NOAEL for risk 

quotient calculation was revised to the next most sensitive endpoint of 200 mg ai/kg-diet, which 

was based on decreases in offspring organ weights (thymus and spleen) and reduced pup body 

weight in the F2 generation. 

Chronic dietary risk quotients were re-calculated with the new chronic endpoint. Risk quotients 

ranged from 0.02 to 3.18 and only three uses exceeded the listed and non-listed species level of 

concern (LOC = 1): 1) hardwoods soil injection/drench (RQ = 1.3), 2) citrus soil drench (RQ = 

1.2), and 3) cucurbits drip irrigation (RQ = 3.2). The risk quotients were calculated using the 

conservative assumption that the mammal would consume 100 percent of its diet from treated 

plants. This assumption likely overestimates exposure because a mammal may not feed 

exclusively on cyantraniliprole-treated plants. Consequently, the potential for direct risk 

concerns to mammals is low, as is the potential for indirect effects to any species that rely on 

affected mammals for food, shelter, or other resources. Tables 1 and 2 present the RQs based on 

the 200 mg ai/kg-diet mammalian NOAEL. 

Table 1. Mammalian Foliar, Bark Spray, and Seed Treatment Chronic Risk Quotients 

(Based on T-REX-Calculated EECs) for Cyantraniliprole 

Feeding Category Mammalian Chronic DietaryBased RQs 

Brassica leafy vegetables, leafy vegetables 

2 apps at 0.175 lb ai/A and 1 app at 0.05 lb ai/A (7 days) 

Short grass 0.40 

Tall grass 0.18 

Broadleaf plants 0.23 

Fruits/pods 0.03 

Arthropods 0.16 

Seeds 0.03 

Brassica leafy vegetables, bushberries, leafy vegetables (except brassica), 

corm and tuberous vegetables, bulb vegetables 

3 apps at 0.133 lb ai/A (5 days) 

Short grass 0.44 

Tall grass 0.20 

Broadleaf plants 0.24 

Fruits/pods 0.03 

Arthropods 0.17 
3 

Feeding Category Mammalian Chronic DietaryBased RQs 

Seeds 0.03 

Citrus, cotton, oil seeds, pome fruit, stone fruit, tree nuts 

3 apps at 0.133 lb ai/A (7 days) 

Short grass 0.42 

Tall grass 0.19 

Broadleaf plants 0.24 

Fruits/pods 0.03 

Arthropods 0.16 

Seeds 0.03 

Cucurbits, fruiting vegetables 

2 apps at 0.175 lb ai/A and 1 app at 0.05 lb ai/A (5 days) 

Short grass 0.42 

Tall grass 0.19 

Broadleaf plants 0.24 

Fruits/pods 0.03 

Arthropods 0.17 

Seeds 0.03 

Potatoes (seed treatment) 

1 app at 0.69 lb ai/A 

Seeds N/A 

Potatoes (seed treatment) 

1 app at 0.176 lb ai/A 

Seeds N/A 

Rapeseed including canola varieties, mustard seed (seed treatment) 

1 app at 0.4 lb ai/A 

Seeds N/A 

Sunflower (seed treatment) 

1 app at 0.016 lb ai/A 

Seeds N/A 

Flowerbeds and groundcovers 

2 apps at 0.208 lb ai/A (7 days) 

Short grass 0.47 

Tall grass 0.21 

Broadleaf plants 0.26 

Fruits/pods 0.03 

Arthropods 0.18 

Seeds 0.03 

Ornamentals treated by commercial and consumer applicators 

2 apps at 0.13 lb ai/A (7 days) 

Short grass 0.29 

Tall grass 0.13 
4 

Feeding Category Mammalian Chronic DietaryBased RQs 

Broadleaf plants 0.16 

Fruits/pods 0.02 

Arthropods 0.11 

Seeds 0.02 

Ornamental plants, fruit and nut trees (non-bearing) and forest seedlings 

grown in greenhouses, lath and shade houses, containers, field nurseries 

and interiorscapes 

1 app at 0.26 lb ai/A and 1 app at 0.16 lb ai/A (14 days) 

Short grass 0.43 

Tall grass 0.20 

Broadleaf plants 0.24 

Fruits/pods 0.03 

Arthropods 0.17 

Seeds 0.03 

Ornamental plants (exterior landscapes and interior plantscapes), trees 

(including non-bearing fruit and nut trees) shrubs, evergreens, bedding 

plants, flowering plants, flowers, foliage plants, groundcovers, vines, interior 

plantscape plants, vegetable transplants (fruiting, leafy, tuberous, corm), 

public health insect control 

1 app at 0.42 lb ai/A 

Short grass 0.50 

Tall grass 0.23 

Broadleaf plants 0.28 

Fruits/pods 0.03 

Arthropods 0.20 

Seeds 0.03 

Turf, golf courses, residential lawns, commercial grounds, parks, 

playgrounds, athletic fields, sod farms, grassy, weedy, mulched, or bare soil 

areas in and around greenhouses, nurseries, interior plantscapes, lath and 

shade houses, under trees and shrubs that are being grown in-ground 

1 app at 0.26 lb ai/A and 1 app at 0.16 lb ai/A (30 days) 

Short grass 0.36 

Tall grass 0.17 

Broadleaf plants 0.20 

Fruits/pods 0.02 

Arthropods 0.14 

Seeds 0.02 

Fly control bait (granular) 

5 apps at 0.087 lb ai/A (7 days) 

Short grass 0.40 

Tall grass 0.18 

Broadleaf plants 0.23 
5 

Feeding Category Mammalian Chronic DietaryBased RQs 

Fruits/pods 0.03 

Arthropods 0.16 

Seeds 0.03 

Table 2. Summary of Mammalian Chronic RQs for Soil Injection/Soil Drench, Potted 

Ornamental Drench, and Agricultural Drip Irrigation for Cyantraniliprole 

Mammalian Chronic 

Dietary-Based RQs 

Soil injection/drench hardwood 0.74 

Soil injection/drench hardwood 1.27*** 

Soil drench (citrus) 1.17*** 

Soil injection/drench softwood 0.34 

Soil injection/drench softwood 0.58 

Potted non-woody ornamental drench 0.02 

Potted non-woody ornamental drench 0.05 

Drip irrigation (brassica vegetables) 0.32 

Drip irrigation (cucurbits) 3.18*** 

Drip irrigation (fruiting vegetables) 0.91 

Drip irrigation (leafy vegetables) 0.27 

Drip irrigation (corm and tuberous vegetables) 0.32 

***Risk quotient exceeds chronic LOC of 1 

Terrestrial Monocots 

The original risk assessment identified potential risk concerns to terrestrial monocots based on an 

absence of seedling emergence data. The vegetative vigor studies indicated that onion was the 

most sensitive monocot; however, acceptable data for onion were not available for the seedling 

emergence endpoint (MRIDs 48120186 and 48122575). The assessment concluded that if the 

onion NOAEC was slightly more toxic (≤ 0.100 lb ai/A) than the current most sensitive seedling 

emergence endpoint (0.134 lb ai/A), risk quotients would exceed the LOC for listed monocots. 

Consequently, risk concerns were presumed. 

As a further clarification, many of the terrestrial plant studies for monocots and dicots were 

judged limited in their quantitative utility because many of the tested species had control 

performance problems. Lower-than-expected performance in controls may indicate a problem 

with the seed stock or environmental conditions; data are not used from such studies because of 

concerns that the poor control performance may mask a valid toxicological effect of the 

pesticide. Consequently, a reduced vegetative vigor and seedling emergence dataset was 

available for terrestrial plants. 

For the vegetative vigor endpoint, an acceptable limit test showed that onions were the most 

sensitive monocot – two times more sensitive than corn, which was the only acceptable monocot 

endpoint available for the seedling emergence test (MRID 48120186). The study authors 

concluded the growth deficits in the onion vegetative vigor test were statistically significant and 

moved to a definitive test. A NOAEC was established for onion at 0.067 lb ai/A, which is half of 
6 

the NOAEC for the most sensitive dicot (cucumber NOAEC = 0.134 lb ai/A). For the seedling 

emergence endpoint, onion was again much more sensitive than corn (MRID 48122575). 

However, the aforementioned control performance problem affected the onion study and thus 

precluded establishing a NOAEC for onion. If the relationship seen between corn and onion in 

the vegetative vigor test is applied to the seedling emergence endpoints, it would be reasonable 

to expect the seedling emergence NOAEC for onion to be lower than corn and the other dicots 

with acceptable data; an endpoint some two fold lower may be a reasonable prediction, based on 

the observed relationship. 

Consequently, in the absence of toxicity information for onion, risk concerns to terrestrial 

monocots cannot be excluded at this time. The risks apply only to listed monocots (direct 

effects) and to other listed species with obligate relationships with a monocot (indirect effects). 

Risks are expected to be limited to monocots near the edge of the field and to taper off as 

distance from the field’s edge increases. A spray drift buffer distance cannot be calculated for 

listed monocots because a precise toxicity value for onion is not available. For reference, if the 

toxicity value is assumed to be half the NOAEC of corn, a spray drift buffer of 20 ft would be 

protective at the maximum application rate of 0.42 lb ai/A. 

Honeybee Acute Toxicity Cyantraniliprole Compared to Other Insecticides 

EFED compiled additional information regarding the toxicity of cyantraniliprole compared with 

alternative registered insecticides. Table 3 reports the highest and lowest acute contact and oral 

toxicity endpoints for the honeybee for several common classes of insecticides (neonicotinoids, 

carbamates, pyrethroids, and organophosphates). Chemical classes are organized alphabetically 

with cyantraniliprole at the bottom of the table. Tables 4 and 5 report acute honeybee toxicity on 

a chemical-by-chemical basis; the table is ranked with the most toxic pesticides at the top and the 

least toxic at the bottom. Insecticides were chosen based on those listed as alternatives to 

cyantraniliprole in the Reduced Risk Rationale that was submitted by the registrants (Baer et al., 

2011; USEPA, 2011 - D392092). Toxicity data are not available for each chemical and/or for 

each exposure route (oral and contact), thus the data do not represent a complete picture of acute 

toxicity to honeybees. Note that lower toxicity values in the table represent insecticides of 

greater toxicity to honeybees. 

Table 3. Summary of Cyantraniliprole, and Other Chemical Classes Acute Toxicity to 

Honeybees 

Chemical Honeybee acute contact (μg 

ai/bee) 

Honeybee acute oral (μg 

ai/bee) 

Carbamates 0.1600 to 35 0.094 to 3.01 

Neonicotinoids 0.024 to <12.5 0.0037 to >10.21 

Organophosphates 0.059 to 58.9 0.056 to 0.44 

Pyrethroids 0.0015 to 0.52 0.172 to 0.909 

Cyantraniliprole 0.55 0.116 

Cyantraniliprole/thiamethoxam 

TEP 

0.058 0.0062 

 
7 

Table 4. Comparison of Acute Contact Toxicity to Honeybees for Cyantranilprole and 

Other Insecticides 

Chemical (Class) Contact LD50 (μg ai/bee) MRID 

Deltamethrin (pyrethroid) 0.0015 42114815 

Spinosad (spinosyn) 0.0029 43414547 

Bifenthrin (pyrethroid) 0.015 VAOTALO1 

Esfenvalerate (pyrethroid) 0.017 41698402 

Cypermethrin (pyrethroid) 0.023 260647 (accession number) 

Permethrin (pyrethroid) 0.024 42674501 

Dinotefuran (neonicotinoid) 0.024 45639727 

Thiamethoxam (neonicotinoid) 0.024 44714927 

Spinetoram (spinosyn) 0.024 46695147 

Cyfluthrin (pyrethroid) 0.037 00153638 

Lambda-cyhalothrin (pyrethroid) 0.038 40052409 

Clothianidin (neonicotinoid) 0.0439 45422426 

Cyantraniliprole/Thiamethoxam 

TEP (diamide/neonicotinoid)* 

0.058 48432530 

Chlorpyrifos (organophosphate) 0.059 05001991 

Dicrotophos (organophosphate) 0.076 05001991 

Imidacloprid (neonicotinoid) 0.078 42273003 

Chlorfenapyr (pyrrole) 0.12 42770233 

Methomyl (carbamate) 0.1600 45093001 

Indoxacarb (oxadiazine) 0.18 44477234 

Malathion (organophosphate) 0.2000 05001991 

Oxamyl (carbamate) 0.31 05001991 

Abamectin (avermectin) 0.408 00159162 

Oxydemeton-methyl 

(organophosphate) 

0.54 05001991 

Cyantraniliprole (diamide) 0.55 48120137 

Phosmet (organophosphate) 1.1 00066220 

Acephate (organophosphate) 1.20 44038201 

Acetamiprid (neonicotinoid) <12.5 44651874 

Trichlorfon (organophosphate) 59.83 00036935 

Chlorantraniliprole (anthranilic 

diamide) 

>100 46889120 

Methoxyfenozide 

(diacyhydrazine) 

>100 44144429 

Flubendiamide (phthalic acid 

diamide) 

>200 46817009 

Spirotetramat (tetramic acid) 1073 46904461 

*Note that the cyantraniliprole-thiamethoxam TEP is less toxic than thiamethoxam alone. 

 
8 

Table 5. Comparison of Acute Oral Toxicity to Honeybees for Cyantraniliprole and Other 

Insecticides 

Chemical (Class) Oral LD50 (μg ai/bee) MRID 

Clothianidin (neonicotinoid) 0.0037 45422426 

Imidacloprid (neonicotinoid) 0.0038 42273003 

Thiamethoxam (neonicotinoid) 0.005 44714927 

Cyantraniliprole/Thiamethoxam 

TEP (diamide/neonicotinoid)* 

0.0062 48432530 

Dinotefuran (neonicotinoid) 0.0076 45639727 

Chlorantraniliprole (anthranilic 

diamide) 

0.0274 46979602 

Cyantraniliprole (diamide) 0.116 48432416 

Cypermethrin (pyrethroid) 0.172 260647 (accession number) 

Methomyl (carbamate) 0.2900 45093001 

Oxydemeton-methyl 

(organophosphate) 

0.31 05001991 

Malathion (organophosphate) 0.3800 05004151 

Lambda-cyhalothrin (pyrethroid) 0.909 40052409 

Acetamiprid (neonicotinoid) >10.21 44651874 

Methoxyfenozide 

(diacyhydrazine) 

>100 44617717 

Spirotetramat (tetramic acid) 607 46904461 

*Note that the cyantraniliprole-thiamethoxam TEP is less toxic than thiamethoxam alone. 

References 

Baer, C.A., T.N. Davis-Cannon, and T.I. McPherson. 2011. Reduced risk rationale for use of 

cyantraniliprole on bushberries, citrus, cotton, oil seeds, pome fruit, stone fruit, tree nuts, 

vegetables (bulb, corm and tuberous, cucurbit, fruiting, leafy brassica, and leafy nonbrassica), and professional products (fly bait, indoor & outdoor insect control for public 

health pests such as cockroaches, ants, flies and termites and nuisance insect pests, 

turfgrass & ornamentals, tree injection and production greenhouse & nursery 

ornamentals). E.I. du Pont de Nemours and Company, Newark, Delaware. 

USEPA, 2011. Reduced Risk Analysis for Cyantraniliprole Use on Bushberries, Citrus, Cotton, 

Oil Seeds, Pome Fruit, Stone Fruit, Tree Nuts, Vegetables (Bulb, Corm and Tuberous, 

Cucurbit, Fruiting, Leafy Brassica, and Leafy Non-Brassica), and Professional Products 

(Fly Bait, Indoor and Outdoor Insect Control for Public Health Pests such as 

Cockroaches, Ants, Flies, and Termites and Nuisance Insect Pests, Turfgrass and 

Ornamentals, Tree Injection, and Production Greenhouse and Nursery Ornamentals). 

Environmental Fate and Effects Division, Office of Pesticide Programs, Environmental 

Protection Agency.